Iron dextran and systemic lupus erythematosus.
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Biomedical subjects
Publications and source records attributed to V M Oh.
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In recent controlled trials using clinic-based manometry, thiazides and beta-blockers prevented cerebrovascular and coronary deaths in patients aged 60-79 years with cryptogenic hypertension (diastolic 90-119 mm Hg). Elderly patients should usually take low-dose thiazide with potassium replacement. beta-Blockers also postpone death, but may mask hypoglycaemia. Calcium blockers and low-dose angiotensin-converting enzyme (ACE) inhibitors appear preferable in diabetes, and thiazides or ACE inhibitors in heart failure or peripheral vascular disease. Maintaining average diastolic pressure at 80-84 mm Hg impairs function of the kidneys, and possibly the myocardium. Metabolic reactions worsen with age. Drug treatment should match individual daily function. By clinic manometry, the protection:risk ratio of antihypertensive treatment progressively decreases with age, reaching less than 1.0 in patients over 80-85 years. Twenty-four-hour ambulatory blood pressure information should guide treatment more reliably in patients greater than or equal to 60 years.
To test the hypothesis that there is an abnormal serum insulin response to a carbohydrate load in thyrotoxic hypokalaemic periodic paralysis (THPP), 18 men with THPP and 15 with uncomplicated thyrotoxicosis were studied during an oral glucose tolerance test. The THPP group had significantly higher fasting insulin concentrations (27.6 [3.6] vs 13.4 [1.8] mU/l; p less than 0.005) and a higher overall insulin response to oral glucose (p less than 0.001 by ANOVA) than the thyrotoxicosis group. There were no significant differences in fasting or stimulated glucose. Hyperinsulinaemia may be an important factor in the precipitation of acute paralysis in THPP.
To determine the effects of age, sex, race, and family history of hypertension on cellular cation transport, we measured specific tritiated-ouabain binding (sodium/potassium pump number), and sodium/potassium pump-mediated rubidium-86 uptake in blood lymphocytes from 105 healthy normotensive adults, comprising 23 Chinese and 19 Indian subjects who had first-degree relatives with cryptogenic hypertension, and 40 Chinese and 23 Indian matched subjects without such history. Both Chinese and Indian subjects with family history had significantly fewer sodium/potassium pumps than control subjects. Sodium/potassium pump-mediated rubidium-86 uptake was similar in these four subject groups. Seven Indian patients with untreated cryptogenic hypertension had fewer sodium/potassium pumps than normotensive Indians without family history. Age did not affect sodium/potassium pump numbers in cells from normotensive subjects. In normotensive subjects without family history. Chinese women had more sodium/potassium pumps than Chinese men, but Indian subjects did not show this pattern. We conclude that a family history of cryptogenic hypertension is associated with fewer lymphocyte sodium/potassium pumps than normal. The reduction in cellular pump number might be only a marker, or an epiphenomenon. However, the reduction in pump number might contribute to the pathogenesis of cryptogenic hypertension if it produces sodium retention in renal tubular or peripheral vascular cells.
Elderly persons are apt to receive multiple drugs for many diseases. Prescribers should take extra care in persons aged over 65-70 years, and especially the very old. The main problem of the elderly is the unpredictability of their response to drugs. Self-medication with both prescribed and over-the-counter drugs worsens this problem. Drug actions may be altered by impairment of the liver, kidneys and brain, or acute illness, or both. Unwanted (adverse) drug reactions often produce rapid and unduly severe illness in the old. Some antibacterial antibiotics like the sulphonamides are best avoided. Taking many drugs together promotes adverse interactions between the drugs. Drugs with a narrow therapeutic ratio, such as warfarin, digoxin, the aminoglycosides, and many antiarrhythmic drugs, cause clinical problems. Old persons respond more abruptly to drugs like benzodiazepines, opioid analgesics, and antiparkinsonian drugs. Anaesthesia given on top of psychotropic drugs may damage the central nervous system. The elderly brain is more sensitive to induction agents and short-acting intravenous anaesthetics, like alfentanil and midazolam; the elderly liver is more easily damaged by inhalational anaesthetics like halothane. The overall benefit:risk ratio should be judged for every drug in each patient. Wherever possible, drug treatment should be avoided. If drugs are given, safe drugs with broad therapeutic ratios and tissue- or receptor-specific actions are preferable. Drug doses are usually, but not always, reduced. Benefit from a drug should be assessed early. Severe unpredictable adverse reactions need immediate cessation of the drug and prompt patient support. The practitioner should frequently review the patient's continuing need for drugs.
A double-blind, balanced and randomised study in 8 healthy volunteers examined the effects of relatively high versus low single doses of practolol on heart rate and ventilation at rest and during standardised exercise. Practolol 1 and 4 mg/kg, a typically non-selective drug propranolol 0.2 mg/kg, and placebo were given intravenously at weekly intervals. Cardiac beta-adrenoceptor blockade was measured by the reduction in exercise heart rate greater than 160 beats/min, and bronchial beta-adrenoceptor blockade by the reduction in exercise peak expiratory flow rate (PEFR) up to 4 h after each treatment. Results were assessed by analysis of co-variance. All three active treatments reduced exercise heart rate markedly, practolol 4 mg/kg causing most reduction. Exercise PEFR was significantly reduced by propranolol 0.2 mg/kg compared with both practolol 1 mg/kg and placebo at all times of measurement, and by practolol 4 mg/kg compared with practolol 1 mg/kg and placebo at most times. Mean plasma concentrations after practolol 4 mg/kg were 3.5 to 4.5 times higher than after 1 mg/kg. Practolol may lose its 'cardioselectivity' and cause airflow obstruction at relatively high plasma concentrations above about 2 microgram/ml.
The potential antidepressant drug ciclazindol inhibited dopamine uptake into human platelets without affecting 5-hydroxytryptamine uptake as compared with a control. It inhibited the tyramine pressor response less than desipramine after single 50-mg oral doses in 6 healthy volunteers under double-blind conditions. Compared with tandamine in a double-blind placebo-controlled study in nine healthy subjects, ciclazindol 50 mg orally caused no significant anticholinergic effects but reduced appetite according to an analysis of variance. Nonparametric analysis did not confirm the anorectic effect. Previous studies had shown that ciclazindol increased glucose uptake into isolated human skeletal muscle independently of insulin. Overall, ciclazindol resembles the antiobesity drug mazindol in molecular structure and pharmacological effects in man. Interactions with sympathomimetic amines and adrenergic neurone-blocking drugs cannot be excluded on the basis of these studies.
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1 The effects of beta-adrenoceptor antagonists given in single doses by oral or intravenous routes were examined in two double-blind controlled studies performed in healthy volunteers. Heart rate and peak expiratory flow rate (PEFR) were measured at rest and during standardized exercise. 2 Propranolol 80 mg and metoprolol 100 mg orally tended to reduce, and propranolol and metoprolol 0.2 mg/kg intravenously did reduce the physiological increase in PEFR during exercise; oxprenolol 80 mg orally and 0.2 mg/kg intravenously did not. Practolol 200 mg orally reduced this increase, but practolol 1 mg/kg intravenously did not. 3 In a third study of similar design, pindolol 0.05 mg/kg intravenously did not affect exercise-induced increase in PEFR. 4 Heart rate during exercise was reduced to a comparable extent at different times by all the active treatments. 5 Oxprenolol and pindolol share with practolol the property of partial agonist activity, which might contribute to their apparent lack of effect on airways resistance. A further possibility is that alpha-adrenoceptor blockade helps to maintain exercise-induced increase in PEFR.
The influence of oral sodium bicarbonate and aluminium hydroxide on the absorption of indomethacin has been studied in normal volunteers. While sodium bicarbonate appeared to increase indomethacin absorption, aluminium hydroxide markedly reduced both the rate and extent of absorption. The buccal absorption of indomethacin over the pH range 5-9 was also studied in normal volunteers, and showed that the percentage absorption increased markedly as the pH was reduced. The clinical importance both of pH-partition and of adsorption are discussed in the context of antacid interactions. It is concluded that caution must be exercised when prescribing an antacid with other orally-administered drugs.
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